The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
Date
2005-12
Authors
Reuter, Helmuth
Journal Title
Journal ISSN
Volume Title
Publisher
Stellenbosch : University of Stellenbosch
Abstract
Mycobacterium tuberculosis (M. tuberculosis) accounts for more adult deaths than
any other infectious agents. The present study included 162 patients with tuberculous
pericarditis; 50% of the tuberculous pericarditis patients studied were human
immunodeficiency virus (HIV) positive, compared to only 4.2% of patients who
presented with non-tuberculous pericardial effusions. A steady year-to-year rise in
HIV prevalence was observed in this 6-year study. Although the prognosis of
pericardial tuberculosis (TB) is excellent with appropriate medical treatment,
untreated pericardial TB has a mortality of 80-85%. It is thus important to diagnose
tuberculous pericarditis efficiently. Traditionally, the diagnosis of pericardial TB is
established by positive mycobacterial culture and/or histological evidence of
necrotising granulomatous inflammation of the pericardium. Our study confirmed the
insensitivity of pericardial fluid culture and pericardial biopsy in the diagnosis of
pericardial TB, and at the time of clinical decision-making, results were usually not
available. To overcome these difficulties, we explored various alternative strategies
and this resulted in two diagnostic tools, namely a diagnostic rule and a diagnostic
algorithm or classification tree.
By means of classification and regression tree analysis, we allocated a weighted
diagnostic index to each of five independently predictive features (fever, night sweats,
weight loss, serum globulin >40 g/L and peripheral blood leukocyte count
<10x109/L). A total diagnostic index of 6 or more corresponded to 82-86% sensitivity
and 76-87% specificity for a diagnosis of tuberculous pericarditis. When possible, pericardial fluid should be aspirated to determine adenosine
deaminase (ADA) levels and pericardial differential leukocyte counts. Fluid should
also be sent for Gram stain and culture. The proposed diagnostic classification tree
utilises the independently predictive attributes of pericardial adenosine deaminase
levels, pericardial fluid lymphocyte/neutrophil ratios, peripheral leukocyte counts and
the HIV status. Applying this prediction model to our entire data set of 233 patients
resulted in 96% sensitivity and 97% specificity for the correct diagnosis of
tuberculous pericarditis.
Generally, patients were critically ill at the time of enrolment; 90% of tuberculous
pericarditis presented with echocardiographic features of cardiac tamponade. Echoguided
percutaneous pericardiocentesis with an indwelling catheter and intermittent
daily aspiration was highly effective and safe. It is likely that the combination of this
drainage technique and the early initiation of anti-tuberculous chemotherapy
contributed to the almost complete absence of constriction in the patients studied, and
our data do not support the routine use of adjunctive corticosteroids in patients with
tuberculous pericarditis.
Tuberculous exudates result from a Th1 mediated immune response characterised by
lymphocyte dominance, significantly elevated levels of gamma-interferon (IFN-γ) and
undetectable levels of interleukin-4 (IL-4). IFN-γ levels were not influenced by HIV
status in spite of the severely diminished pericardial CD4+ lymphocyte counts
observed in this study. It is thus likely that in HIV positive patients IFN-γ production
is partly maintained by activated CD8+ T cells, which were significantly elevated in
HIV positive patients compared to HIV negative tuberculous pericarditis patients. This finding underlines the importance of IFN-γ in the human immune response
against M. tuberculosis. We also demonstrated that the presence of ADA in
pericardial fluids reflects the activity of the cellular immune response. Both IFN-γ and
ADA can be utilised as sensitive and specific diagnostic tools for pericardial TB.
Description
Thesis (DMed (Medicine. Internal Medicine))-University of Stellenbosch, 2005.
Keywords
HIV infections, Tuberculosis -- Immunological aspects, Tuberculosis -- Treatment, Mycobacterium tuberculosis, Dissertations -- Internal medicine, Theses -- Internal medicine